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Limitations of a uniform two-fold criterion in the Ames test: Insights from historical control distributions in frameshift-detecting Salmonella typhimurium strains TA97, TA97a, and TA1537.

Created on 12 Sep 2026

Authors

Tsuneo Hashizume, Yoko Inoue, Yuka Sakai, Toru Ishii, Yasunori Takahashi, Yasuyoshi Miura

Published in

Mutation research. Genetic toxicology and environmental mutagenesis. Volume 914. Pages 503955. Epub Aug 12, 2026.

Abstract

In the bacterial reverse mutation (Ames) test, Salmonella typhimurium strains TA1537, TA97, and TA97a are generally regarded as interchangeable for detection of frameshift mutations. A uniform two‑fold increase criterion, vs. the concurrent negative control, is commonly applied when using these strains, without consideration of strain-specific background characteristics. To investigate control criteria applicability, we analyzed negative-control revertant counts for TA97, TA97a, and TA1537, using data from 20 independent experiments, conducted with and without metabolic activation. TA97 and TA97a showed higher mean negative-control counts than TA1537 but exhibited narrower variability, when assessed using historical control ranges defined as the mean ± 2 standard deviations. The upper limits of these ranges corresponded to approximately 1.12-1.45‑fold × the mean for TA97 and TA97a, whereas wider relative ranges were observed for TA1537. These findings indicate that the applicability of a two‑fold increase criterion differs among frameshift‑detecting strains and that interpretation of TA97 and TA97a data may benefit from strain‑specific historical-control data rather than relying solely on a uniform threshold.

PMID:
42727996
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.

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